The context in which a sensory experience occurs can strongly influence whether it is perceived as pleasurable or aversive. In Drosophila, the volatile lipid pheromone cis-vaccenyl acetate (cVA) is produced by males and transferred to females during mating. When presented on eggs laid at food sources, it acts as an attractant. When presented on a mature female, it causes both instantaneous and long-term suppression of male courtship. In both of these situations the presence of another odor dictates the behavioral response to cVA. Our overall goal is to understand how olfactory context can change the immediate effects of a pheromone and lead to long-term changes in behavior. In this grant we will define the circuitry that is involved in sensing cVA and courtship-stimulating pheromones and identify the mechanisms that integrate pheromone signals to create appropriate modulation of courtship initiation. We will use genetically encoded probes of neuronal activity to assess the contribution of local antenna! lobe circuits to association of these cues. These experiments will provide insights into how odor information is processed and into howolfacotry memory is formed. Research in invertebrate model systems has arguably been the driver of the field of molecular memory in mammals. The high degree of structural and molecular conservation in the olfactory system and in mechanisms of learning makes work on olfactory plasticity in Drosophila germane to human health for the many developmental and acquired conditions that affect learning and memory. Specific aims are: 1. Define the olfactory neuron inputs that are required for sensing cVA and courtship-stimulating female pheromones. 2. Investigate the mechanisms of association between stimulatory pheromones and cVA in the antennal lobe. 3. Investigate the mechanisms of context integration in the antennal lobe. 4. Characterize the role of dTrpAl, a non-specific cation channel, in suppression of male-male courtship (collaboration with Garrity Lab). The olfactory system of Drosophila and the molecular basis of learning in this organism are highly homologus to that of humans. Understanding of the cellular mechnaism of olfactory learning in this organism will provide valuable information that can be used in designing therapeutics for human disorders of cognition such as Alzheimer's disease and mental retardation.